Poziotinib reduces tumour size in patients with previously treated HER2 mutation positive non-small-cell lung cancer

1. Almost 30% of patients had an objective response rate, with roughly three-quarters experiencing a reduction in tumour size.

2. Treatment-related adverse events were common and included rash, diarrhea, and stomatitis.

Evidence Rating Level: 2 (Good)

Study Rundown: Between two and five percent of non-small-cell lung cancers (NSCLC) have insertion mutations in the Erb-b2 receptor tyrosine kinase 2 gene (HER2). Effective treatment options are limited for these patients. The tyrosine kinase inhibitor (TKI) poziotinib has previously shown antitumour activity targeting this mutation. This study explored the outcome on tumour response rate, progression-free survival (PFS), and safety in adult patients with HER2 exon 20 insertion-positive NSCLC receiving poziotinib. Objective response rate was 27.8% and 74.4% of patients experienced a reduction in tumour size. Median PFS was 5.5 months with 37.8% of patients remaining progression-free 6 months later. Adverse events were common, with almost all patients experiencing adverse events (AE) related to treatment. The most common AE was rash, followed by diarrhea and stomatitis. Grade 3 adverse events occurred in 78.9% of patients. Limitations to this study include the relatively small sample size and the lack of a control group for comparison. Overall, patients with HER2 mutation-positive NSCLC may benefit from treatment with poziotinib.

Click to read the study in The Journal of Clinical Oncology

Relevant Reading: HER kinase inhibition in patients with HER2- and HER3-mutant cancers

In-Depth [randomized controlled trial]: This multicentre, phase 2 study (ZENITH20) had 90 patients with previously treated HER2 exon 20 insertion mutation-positive NSCLC, who received poziotinib. The primary outcome was objective response rate with progression-free survival (PFS) and safety being secondary outcomes. Objective response rate was 27.8% (95% confidence interval (CI), 18.9-38.2%). Reduced tumour size was found in 67 of 90 patients (74.4%). Median PFS was 5.5 months (95% CI, 3.9-5.8 months). At 6 months, 37.8% remained progression-free (95% CI, 25.5-50.0%). 97.8% of patients reported adverse events (AE) due to treatment, the most common of which were rash (91.1%). Diarrhea and stomatitis were also common, with 82.2% and 68.9% of patients experiencing them, respectively. AE caused treatment cessation in 13.3% of patients. 71 patients experienced grade 3 AEs and four experienced grade 4 AEs, which included electrolyte derangements such as hypocalcemia, hypomagnesemia and others included stomatitis, pancreatitis and dyspnea. One patient had a grade 5 pneumonia AE.

Image: PD

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